Stabilizing arterial blood gas tensions and blood and brain acidity is the major function of the ventilatory system. A large investment of effort has been expended on the control system characteristics responsible for the responses to abnormal inhaled gas mixtures. This has resulted in a generally clear understanding of the control scheme operative under these conditions. We are however, in large part, ignorant of how breathing is controlled in responses to more normal stresses to the blood gas and acid-base system, such as changes in metabolic rate during exercise, dietary alterations and lung disease. We plan to determine, in the coming year, the extent to which exercise hyperpoxia is a CO2-linked phenomenon. To accomplish this we will use extracorporeal gas exchange to remove the CO2 produced metabolically during exercise while leaving O2 exchange normal. With CO2 return to the lung being at control level, dose ventilation return to control levels? If so, CO2 is the mechanism; if not, the residual increase is the proportion of non-CO2 drive. Also, by regional stimulation of the brain in anesthetized dogs, we plan to determine the role of the carotid bodies in the coupling between the cardiovascular and ventilatory systems.